Haematological effects of running. A brief review.
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Biomedical subjects
Publications and source records attributed to B J Miller.
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The development of autoimmune type 1 diabetes mellitus in man and the nonobese diabetic (NOD) mouse is greatly influenced by a gene linked to the MHC. Although homozygosity at the NOD MHC is required for a high prevalence of disease, during backcross studies we have found a small number of diabetic H-2nod/b MHC heterozygotes. These diabetic heterozygotes could either represent a crossover event between the MHC and a putative MHC-linked diabetogenic gene or, alternatively, they could indicate that there is a dominant MHC-linked diabetic gene that has low penetrance in the heterozygous state. Pedigree analysis of a diabetic H-2nod/b MHC heterozygote favors the latter hypothesis.
Three studies were performed to assess more accurately the prevalence, natural history, and appropriate treatment of acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma involving ocular structures. The first study was a prospective examination of 100 male homosexuals with AIDS-related Kaposi sarcoma for signs of ophthalmic involvement. Of the 20 patients who had ophthalmic lesions, 16 had eyelid lesions and seven had conjunctival lesions. In four patients, the ophthalmic lesion was the first, and initially the only, clinically identified manifestation of Kaposi sarcoma. The second study was a retrospective review of all patients with ophthalmic Kaposi sarcoma examined at one institution over a six-year period to determine its natural history and response to therapy. Most lesions were slowly progressive and responded to systemic drug therapy. Six patients were successfully treated with radiation therapy to prevent complications. The third study was a retrospective review of all patients with AIDS-related ophthalmic Kaposi sarcoma treated with local irradiation by one radiation oncologist. Each of 12 patients showed a response to treatment, and ten had a complete resolution of lesions, but recurrences were common. Side effects included skin erythema in six patients and hair loss in one patient. For local treatment of ophthalmic Kaposi sarcoma, irradiation appears to be safe and effective for palliative therapy.
In the first experiment, copulations in 10 domestic ferrets were interrupted 5 minutes after penetration. Ten control females were bred without interruption to the same males. Both control and experimental animals were rebred in the same manner to the same males 24 hours later. Sperm were present in all postcoital washes. We allowed all females from the first experiment to proceed to their expected date of parturition. All females who had been interrupted during copulation failed to conceive, whereas all controls produced litters. In a second experiment, the same procedure was followed; however, in this experiment, ferret oviducts and uteri were flushed 10 days after copulation. Nine control females (one failed to ovulate) averaged 5.2 blastocysts (range 2-10; S.D. = 5.8) per animal. Of nine interrupted copulation ferrets (one failed to ovulate), only one animal produced a single blastocyst. The interrupted copulation group averaged 4.4 unfertilized eggs (range 2-10; S.D. = 5.0) per female. Although ferrets ovulated during short copulations, those eggs are not likely to be fertilized.
Differences in volatile N-nitrosamines (NNAs) found in nitrite-cured bacon cooked in an electric skillet and a microwave oven were determined. Samples of bacon were fried in an electric skillet at 171 and 206 degrees C and in a standard microwave oven (rated at 700 W full power) for 45 and 75 sec/slice. The level of NNAs were determined in the cooked bacon and fried-out fat by using gas chromatography-thermal energy analysis. Both N-nitrosopyrrolidine (NPYR) and N-nitrosodimethylamine (NDMA) were detected in the fried-out bacon fat at levels up to 20.8 and 23.3 ng/g, respectively. The total NNAs (NDMA and NPYR) in the skillet-fried bacon was c. 11 ng/g for both the 171 and 206 degrees C fried samples. No NNAs were detected in the bacon or fried-out fat after cooking in a microwave oven for 45 sec/slice. However, excessive cooking of the bacon in a microwave oven (75 sec/slice) does produce levels of NPYR up to 5 ng/g. The minimum detectable level of NPYR was 2.08 ng/g and that of NDMA was 0.76 ng/g. These results indicated that the method of cooking meats containing nitrite could affect the level of NNAs in the cooked product, thereby affecting the level of human exposure to NNAs.
The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by at least three recessive loci, including one linked to the MHC. To determine whether any of these genetic loci exert their effects via the immune system, radiation bone marrow chimeras were constructed in which (NOD X B10)F1-irradiated recipients were reconstituted with NOD bone marrow cells. Unmanipulated (NOD X B10)F1 mice, or irradiated F1 mice reconstituted with F1 or B10 bone marrow, did not display insulitis or diabetes. In contrast, insulitis was observed in a majority of the NOD----F1 chimeras and diabetes developed in 21% of the mice. These data demonstrate that expression of the diabetic phenotype in the NOD mouse is dependent on NOD-derived hematopoietic stem cells. Diabetogenic genes in the NOD mouse do not appear to function at the level of the insulin-producing beta cells since NOD----F1 chimeras not only developed insulitis and diabetes but also rejected beta cells within pancreas transplants from newborn B10 mice. These data suggest that the beta cells of the NOD mouse do not express a unique antigenic determinant that is the target of the autoimmune response.
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The nonobese diabetic mouse is a model of spontaneous type I diabetes mellitus. It is possible to induce diabetes in young, irradiated nonobese diabetic mice by using adoptive transfer of splenocytes or splenic T cells obtained from diabetic donors. This study demonstrates that the induction of diabetes in the adoptive transfer system is dependent on both the L3T4+ and Lyt-2+ subsets of T cells. Neither of these T cell subsets alone mediates the development of severe insulitis or diabetes when adoptively transferred to young, irradiated recipients. In addition, we show that both the L3T4+ and Lyt-2+ subsets must be obtained from diabetic donors in order to transfer diabetes; neither subset can be replaced with cells obtained from young, nondiabetic donors.
During a 10-day 5 degrees C storage and subsequent 4-6-hr 37 degrees C incubation, both percent live spermatozoa and percent spermatozoa with an intact acrosome decreased, and percent spermatozoa with a late-reacted or without an acrosome increased. When stored spermatozoa were mixed with oocytes, no decrease in percent of oocytes with spermatozoa bound or percent of oocytes with spermatozoa starting to penetrate occurred as storage time increased. A 58% decrease in acrosin gelatinolytic activity and a 56% decrease in acrosin esterolytic activity but no decrease in nonacrosin proteolytic activity were evident over the 10-day storage. These studies show that a change in acrosomal morphology as well as a loss of acrosin may be responsible for the decreased fertility following extended in vitro storage of mammalian spermatozoa.
5-Halo-6-phenyl pyrimidinones, represented by 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and 2-amino-5-iodo-6-phenyl-4(3H)-pyrimidinone (AIPP), and 8-substituted guanosines, represented by 8-bromoguanosine (8-BrGuo) and 8-mercaptoguanosine (8-MGuo), are well-documented biological response modifiers. We have found that these substituted pyrimidinones and guanosines are very similar in their abilities to activate B cells. ABPP, AIPP, 8-BrGuo, and 8-MGuo induced murine B cells to polyclonally proliferate and differentiate in vitro. The maximal B-cell response levels and the kinetics of the responses elicited with both classes of compounds were comparable; however, ABPP and AIPP were approximately 10-fold more potent than 8-BrGuo and 8-MGuo. An additional similarity observed between the two classes was that polyclonal activation of B cells by ABPP, AIPP, 8-BrGuo, and 8-MGuo was limited to large B cells which had probably been activated previously in vivo. This is in contrast to lipopolysaccharide which is capable of inducing both large, activated B cells and small, resting B cells to proliferate and differentiate. Although substituted pyrimidinones and guanosines were not able to induce new DNA synthesis or antibody production in small B cells, both classes of compounds increased the expression of Ia antigens on the surface of both small and large B cells. These data, together with the recent observations that 8-BrGuo, like ABPP and AIPP, can stimulate NK and cytotoxic macrophage activity via the induction of interferon, strongly suggest that 5-halo-6-phenyl pyrimidinones and 8-substituted guanosines belong to the same structural class of biological response modifiers. Thus, the residues held in common by these two classes of stimulators may interact with the same cellular constituent in the target cells.
This study was designed to examine the relationship between foot impact force and the magnitudes of the changes in markers of intravascular hemolysis during distance running. Fourteen male distance runners (VO2 max = 66.1 +/- 5.0 ml.kg-1.min-1, mean +/- SD) completed two treadmill runs and a resting control procedure. The two treadmill tests involved running at 215 m.min-1 for 10,000 footstrikes at elevations of either +6% (uphill) or -6% (downhill). Mean foot impact force was 11% greater with the downhill than the uphill running. The three procedures were ordered randomly and separated by 7 days. Hemoglobin concentration (Hb), hematocrit (Hct), plasma free hemoglobin (PFHb), and haptoglobin (Hp) concentrations were assayed in blood samples collected via venipuncture 15 min and immediately before exercise, and immediately, 1 h, and 2 h after the exercise. Repeated measures ANOVA revealed that Hp was significantly decreased and PFHb was significantly increased after treadmill running (P less than 0.05) and that these changes were significantly greater with downhill than uphill running (P less than 0.05). These findings support the theory that mechanical trauma to red blood cells occurring at footstrike is a major cause of hemolysis during running.
This study examines the usefulness of peritoneovenous shunts through a retrospective review of the charts of 16 patients who received this shunt at the University Hospital in Saskatoon up to May 1987. Fourteen shunts were placed for malignant ascites, 1 for alcoholic cirrhosis and 1 for nephrogenic ascites. All patients had symptoms related to abdominal pressure or dyspnea. Diuretics were most frequently used as initial management, and paracentesis was performed to relieve symptoms in all but one patient. However, a trial of sodium restriction was used in only eight patients, and only five of these trials lasted longer than 1 week. Thus, the adequacy of medical management was questionable. The death of one patient was directly attributable to the shunt, and the deaths of four others were suspected to be sequelae of surgery or shunting. Only five shunts were functioning at the time the patient died. In this study, the majority of the patients received little benefit from the peritoneovenous shunt.
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Genetic analysis of the development of diabetes and insulitis has been performed in the nonobese diabetic (NOD) mouse strain, a model of insulin-dependent (type I) diabetes mellitus. (NOD X C57BL/10)F1, F2, and (F1 X NOD) first-, second-, and third-backcross generations were studied. The data obtained were consistent with the hypothesis that diabetes is controlled by at least three functionally recessive diabetogenic genes, or gene complexes, one of which is linked to the MHC of the NOD. In contrast, pancreatic inflammation leading to insulitis was found to be controlled by a single incompletely dominant gene. One of the two diabetogenic loci that is not linked to the MHC appears to be essential for the development of severe insulitis. This diabetogenic gene may be identical to the gene that controls the initiation of the autoimmune response that progresses to insulitis. Although this gene appears to be functionally recessive in its control of diabetes, it is incompletely dominant in its control of insulitis. The MHC-linked diabetogenic gene, although not required for the development of insulitis, apparently influences the progression of the autoimmune response since NOD MHC homozygotes in the backcross generations displayed the highest incidence and most severe cases of insulitis. Interestingly, we have found two MHC heterozygous backcross females that have become diabetic, suggesting that either the MHC-linked diabetogenic gene is not strictly recessive or that a recombination event has occurred between the diabetogenic gene and the K or I-A regions of the MHC. The third diabetogenic locus appears to influence the progression of severe insulitis to overt diabetes. In animals homozygous at this locus, diabetes may result from a decreased ability to develop a protective suppressor response to the autoimmune process.
Previous studies have documented the ability of 8-bromoguanosine (8-BrGuo) and 8-mercaptoguanosine (8-MGuo) to induce polyclonal proliferation and differentiation of B cells from a variety of mouse strains. In the present study, we have defined the cellular target of this mitogenic activity. Using B cells fractionated according to size, we have found that large B cells are responsive to 8-BrGuo- and 8-MGuo-induced proliferation and differentiation whereas small, resting B cells are relatively unresponsive to these compounds. Addition of splenic adherent cells to the small B-cell fraction partially restored the proliferative but not the differentiative responses to 8-BrGuo and 8-MGuo. Although small B cells alone did not proliferate or differentiate in response to 8-BrGuo and 8-MGuo, cell surface expression of Ia antigens increased following incubation with these compounds. Thus, the biological activity of 8-BrGuo and 8-MGuo appears to be dictated by the cell type upon which it is acting. Small B cells are activated as evidenced by increased levels of surface Ia whereas large B cells are not only activated but are also induced to proliferate and differentiate.
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Recent advances in orthopedic surgery have reawakened interest in the use of osteochondral allografts. A case is presented of a 32-year-old man who was spared a hemipelvectomy for a huge chondrosarcoma of the pelvis by receiving a massive pelvic allograft. This is apparently the first report of such a procedure being performed in Canada. A history of allografting as well as the fate and immunologic aspects of bone grafts are presented. Bone-banking procedures and the clinical application of allografts in 1986 are discussed.
For several years opioids have been given epidurally with success to control chronic intractable pain. The authors report their 2-year experience with internalization of the epidural catheter and injection port in 18 patients at University Hospital, Saskatoon. In all, 21 devices were used. All patients had metastatic cancer; 16 are now dead. The need for other medications was eliminated with 9 and reduced with 12 devices. In the patients who died, the devices were effective for 82% of their remaining life-span. They were able to spend 46% of this time at home. Blockage of the epidural end of the device was the most common mechanical problem, followed by leakage from the port. One patient suffered meningitis after 11 days as a result of subarachnoid placement of the catheter but responded to removal of the device and antibiotic therapy. The authors have been impressed with the excellent pain relief afforded to many of these patients, and their ability to enjoy life free of the sedative effects of other methods of narcotic administration.